This test analyzes the STK11 gene, which is associated with Peutz-Jeghers syndrome (PJS). PJS is a cancer predisposition syndrome characterized by mucocutaneous pigmentation, numerous precancerous polyps in the gastrointestinal tract, and an increased risk of developing a variety of cancers.
Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.
Peutz-Jeghers syndrome can also be ordered as part of a broader panel to test for different types of hereditary cancer, including breast and ovarian, colon, and pancreatic cancers. Depending on the individual’s clinical and family history, one of these broader panels may be appropriate. Any of these broader panels can be ordered for no additional charge.
Peutz-Jeghers syndrome (PJS) is a cancer predisposition syndrome characterized by the development of numerous precancerous polyps in the gastrointestinal tract and an increased risk of developing a wide variety of cancers, including colorectal, pancreatic, stomach, small bowel, and lung. Women with PJS also have increased lifetime risk of breast, ovarian, cervical, and uterine cancers. PJS is characterized by hyperpigmentation of the mucous membranes, which causes freckling around the mouth, eyes, nose, and perianal area. Hyperpigmentation is also common on the fingers.
Essentially everyone with a pathogenic STK11 variant will manifest symptoms of PJS. PJS is also highly variable, meaning individuals with the same condition may present differently, even among family members. Because we cannot predict which cancers may develop, additional medical management strategies focused on cancer prevention and early detection may benefit most patients who are found to have a pathogenic variant.
|Cancer type||Lifetime risk|
|Cervical (adenoma malignum)||10%|
Approximately 80%-94% of individuals with a clinical diagnosis of PJS have an identifiable pathogenic variant in the STK11 gene.
PJS is inherited in an autosomal dominant pattern. Approximately 45% of affected individuals have no family history of PJS, but the proportion of cases due to spontaneous de novo mutations is unclear.
The prevalence of PJS is estimated to be 1 in 50,000 to 1 in 200,000 individuals.
Analysis of the STK11 gene may be considered in individuals with the following features:
Clinical diagnostic criteria for PJS have also been proposed:
For management recommendations, please refer to:
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|